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Incorporating fluorescence cystoscopy for the diagnosis of bladder cancer into clinical practice

Nature Clinical Practice Urology volume 5, pages 424–425 (2008)Cite this article

In the Western World, transitional cell carcinoma (TCC) of the bladder represents the fourth most frequently diagnosed malignancy,1 and in 2008 an estimated 68,810 new incidences of TCC of the bladder will be diagnosed in the US.2 Of the patients newly diagnosed with bladder cancer, approximately 80% present with a non-muscle-invasive tumor.3 A wide range of recurrence and progression rates exists in patients with bladder cancer, and these rates depend largely on the number of tumors initially identified, tumor size, prior recurrence rate, T category, tumor grade and concomitant carcinoma in situ (CIS). According to data from the European Organisation for Research and Treatment of Cancer (EORTC), the probability of recurrence at 5 years after diagnosis is 31–78%, and the probability of disease progression at 5 years is <1%–45%.4 These high recurrence and progression rates have resulted in long-term surveillance and therapy for patients with bladder cancer, making TCC of the bladder the fifth most expensive cancer in terms of total medical care expenditures (almost $3.7 billion in 2001 in the US).5

If a diagnosis of TCC of the bladder is suspected, urinary cytology followed by white-light cystoscopy of the bladder is performed. Although white-light cystoscopy is reliable in the detection of exophytic tumors, it often fails to detect CIS and multifocal flat lesions. Early detection of these cancerous lesions and complete resection are of paramount importance for patients' prognosis. Several attempts have been made, therefore, to overcome the limitations of white-light cystoscopy, and fluorescence cystoscopy is the most promising tool in this regard. Since the early 1990s, 5-aminolevulinic acid (ALA) has been investigated for use in the fluorescent detection of TCC of the bladder. After intravesical application of ALA, protoporphyrin IX accumulates in urothelial cancer cells. Using blue light, malignant lesions fluoresce with an intense red color, in contrast to normal mucosa, which does not fluoresce. High concentrations of ALA must be instilled for 2.5 h to be effective, because ALA has a low diffusion rate across cell membranes. By contrast, a hexyl ester of ALA, hexaminolevulinic acid (HAL), produces at least twice the fluorescence of ALA but at a concentration 45 times lower. Furthermore, the effect of fluorescence is reached much faster; therefore, 1 h of HAL instillation is now current practice. Fluorescence cystoscopy has an excellent safety profile, and can easily be added to standard cystoscopy without the risk of complication.1

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References

  1. Jocham D et al. (2005) Improved detection and treatment of bladder cancer using hexaminolevulinate imaging: a prospective, phase III multicenter study. J Urol 174: 862–866

    Article  Google Scholar 

  2. National Cancer Institute [www.cancer.gov/cancertopics/types/bladder]

  3. Burger M et al. (2007) Photodynamic diagnostics and noninvasive bladder cancer: is it cost-effective in long-term application? A Germany-based cost analysis. Eur Urol 52: 142–147

    Article  Google Scholar 

  4. Sylvester RJ et al. (2006) Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2,596 patients from seven EORTC trials. Eur Urol 49: 466–475

    Article  Google Scholar 

  5. Botteman MF et al. (2003) The health economics of bladder cancer: a comprehensive review of the published literature. Pharmacoeconomics 21: 1315–1330

    Article  Google Scholar 

  6. Daniltchenko DI et al. (2005) Long-term benefit of 5-aminolevulinic acid fluorescence assisted transurethral resection of superficial bladder cancer: 5-year results of a prospective randomized study. J Urol 174: 2129–2133

    Article  CAS  Google Scholar 

  7. Filbeck T et al. (2002) Clinically relevant improvement of recurrence-free survival with 5-aminolevulinic acid induced fluorescence diagnosis in patients with superficial bladder tumors. J Urol 168: 67–71

    Article  Google Scholar 

  8. Denzinger S et al. (2007) Clinically relevant reduction in risk of recurrence of superficial bladder cancer using 5-aminolevulinic acid-induced fluorescence diagnosis: 8-year results of prospective randomized study. Urology 69: 675–679

    Article  Google Scholar 

  9. Hungerhuber E et al. (2007) Seven years' experience with 5-aminolevulinic acid in detection of transitional cell carcinoma of the bladder. Urology 69: 260–264

    Article  Google Scholar 

  10. Fradet Y et al. (2007) A comparison of hexaminolevulinate fluorescence cystoscopy and white light cystoscopy for the detection of carcinoma in situ in patients with bladder cancer: a phase III, multicenter study. J Urol 178: 68–73

    Article  Google Scholar 

  11. Grossman HB et al. (2007) A phase III, multicenter comparison of hexaminolevulinate fluorescence cystoscopy and white light cystoscopy for the detection of superficial papillary lesions in patients with bladder cancer. J Urol 178: 62–67

    Article  Google Scholar 

  12. Denzinger S et al. (2008) Bladder preservation or initial cystectomy in T1G3 bladder cancer: which parameters help in therapeutic decision-making? [German] Aktuelle Urol 39: 58–61

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr Herbert Stepp who had a great role in the development of the currently used fluorescence endoscopy technology.

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Authors and Affiliations

  1. and CG Stief is a Professor and Chairman of the Department of Urology, A Karl is a Post-Graduate Year 5 Urology Resident, D Zaak is an Associate Professor, Ludwig-Maximilians-University, Munich, Germany.,

    Alexander Karl, Dirk Zaak & Christian G Stief

  2. A Karl is also currently working as an Oncology Research Fellow at the University of California at San Francisco, San Francisco, CA, USA.,

    Alexander Karl

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  1. Alexander Karl
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  2. Dirk Zaak
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  3. Christian G Stief
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Correspondence to Alexander Karl.

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Competing interests

A Karl and D Zaak have acted as investigators on a study supported by Photocure, and have received honoraria from GE Medical and Photocure. D Zaak has also received honoraria from medac GmbH. CG Stief declared no competing interests.

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Karl, A., Zaak, D. & Stief, C. Incorporating fluorescence cystoscopy for the diagnosis of bladder cancer into clinical practice. Nat Rev Urol 5, 424–425 (2008). https://doi.org/10.1038/ncpuro1150

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